Lack of NMDA receptor involvement in caffeine-induced locomotor stimulation and tolerance in rats.
The involvement of NMDA-type glutamate receptors in caffeine's locomotor stimulant effects and the development of tolerance to these effects was examined in rats. Caffeine and the noncompetitive NMDA receptor antagonists, MK-801 and phencyclidine (PCP), were examined alone and in combination. Caffeine produced a biphasic dose-effect curve. Both MK-801 and PCP increased locomotor activity at the highest doses tested. MK-801 and PCP shifted the caffeine curve upward, but only with the highest doses that increased locomotor activity when given alone. For the tolerance experiment, osmotic pumps containing either MK-801 or nothing at all and were implanted in rats that were given either caffeinated or drug-free tap water to drink. All rats drinking caffeine showed tolerance to its locomotor stimulant effects, whereas rats drinking drug-free tap water did not. Chronic infusion of MK-801 (0.1 and 0.3 mg/kg/day) failed to block the development of tolerance to caffeine. The 0.3 mg/kg/day infusion of MK-801 appeared to slightly delay the development of tolerance to caffeine, but this effect was probably due to the locomotor stimulant effects of this infused dose of MK-801 alone. These data provide no evidence that NMDA-type glutamate receptors play a crucial role in mediating caffeine's locomotor stimulant effects or tolerance to these effects.
Powell
K R
KR
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Holtzman
S G
SG
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013268:Stimulation, Chemical; D013997:Time Factors
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D002110:Caffeine; D016291:Dizocilpine Maleate